Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYKP5G0)

• DOT Name: Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2)
• Synonyms: EC 2.6.1.16; D-fructose-6-phosphate amidotransferase 2; Glutamine:fructose-6-phosphate amidotransferase 2; GFAT 2; GFAT2; Hexosephosphate aminotransferase 2
• Gene Name: GFPT2
• UniProt ID: GFPT2_HUMAN
• EC Number: 2.6.1.16
• Pfam ID: PF13522 ; PF01380
• Sequence:
  MCGIFAYMNYRVPRTRKEIFETLIKGLQRLEYRGYDSAGVAIDGNNHEVKERHIQLVKKR
  GKVKALDEELYKQDSMDLKVEFETHFGIAHTRWATHGVPSAVNSHPQRSDKGNEFVVIHN
  GIITNYKDLRKFLESKGYEFESETDTETIAKLIKYVFDNRETEDITFSTLVERVIQQLEG
  AFALVFKSVHYPGEAVATRRGSPLLIGVRSKYKLSTEQIPILYRTCTLENVKNICKTRMK
  RLDSSACLHAVGDKAVEFFFASDASAIIEHTNRVIFLEDDDIAAVADGKLSIHRVKRSAS
  DDPSRAIQTLQMELQQIMKGNFSAFMQKEIFEQPESVFNTMRGRVNFETNTVLLGGLKDH
  LKEIRRCRRLIVIGCGTSYHAAVATRQVLEELTELPVMVELASDFLDRNTPVFRDDVCFF
  ISQSGETADTLLALRYCKDRGALTVGVTNTVGSSISRETDCGVHINAGPEIGVASTKAYT
  SQFISLVMFGLMMSEDRISLQNRRQEIIRGLRSLPELIKEVLSLEEKIHDLALELYTQRS
  LLVMGRGYNYATCLEGALKIKEITYMHSEGILAGELKHGPLALIDKQMPVIMVIMKDPCF
  AKCQNALQQVTARQGRPIILCSKDDTESSKFAYKTIELPHTVDCLQGILSVIPLQLLSFH
  LAVLRGYDVDFPRNLAKSVTVE
• Function: Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins.
• Tissue Specificity: Highest levels of expression in heart, placenta, and spinal cord.
• KEGG Pathway:
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
  Insulin resistance (hsa04931)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway: Synthesis of UDP-N-acetyl-glucosamine (R-HSA-446210)

Molecular Interaction Atlas (MIA) of This DOT

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[16]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[11]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[18]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Glutamine--fructose-6-phosphate aminotransferase 2 (GFPT2).	[19]

References

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• [11] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [12] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
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• [19] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.